Quantitative elasticity measurements reveal intratumoral changes in response to antiangiogenic therapy - preliminary results

Abstract

Vascular endothelial growth factor (VEGF) driven tumor neovasculature is known to be hyperpermeable, which in turn raises tumor interstitial fluid pressure and compromises delivery of chemotherapeutic agents. Antiangiogenic therapies inhibit the VEGF signaling pathway leading to increased intratumoral necrosis. The objective of this study was to measure changes in both tumor interstitial pressure and elasticity in response to antiangiogenic therapy. Forty nude athymic mice were implanted with adenocarcinoma cells in the mammary fat pad (20 controls and 20 in therapy group). The therapy mice group was administered bevacizumab three weeks thereafter. Ultrasound imaging (4 mice per group) was performed at days 0.1, 1, 3, and 6 with a Siemens Acuson S2000 system equipped with a 4V1 transducer. Repeated intratumoral elasticity measurements were acquired using the Virtual Touch feature. Subsequently, intratumoral pressure was measured using a needle-based device prior to mouse euthanasia. On average, control tumors grew larger (+7.2%) than bevacizumab-treated tumors (-29.2%). Quantitative elasticity measurements revealed that tumors treated with bevacizumab became much stiffer compared to controls. Matched intratumoral pressure measurements showed a precipitous decrease and peak at day 1 in the therapy group that trended towards zero change thereafter. Alternatively, control tumors exhibited only a slight increase in intratumoral pressure between days 1 and 6 matching the pattern observed in elasticity measurements from this same group. No correlation was found between matched tumor volume and elasticity measurements suggesting that tumor size did not impact elasticity measurements. Overall, this study indicates that quantitative elasticity measurements may be an adjunct indicator for assessing breast cancer response or no response to antiangiogenic therapy.

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“…However, this difference was not statistically significant (p00.1116). Hoyt and Warram [14] , also reported similar observation stiffness of metastases varied according to their primary tumour with mean stiffness (35.89±12.55 kPa).…”